Targeted Antagonism of Vascular Endothelial Growth Factor Reduces Mortality of Mice with Acute Respiratory Distress Syndrome

Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function of the respiratory barrier.However,systemic application of VEGF antagonists would lead to animal death.This study attempts to study the targeted drug delivery for ARDS.In this study,we used soluble fims-like tyrosine kinase-1(sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue.Ninety male BALB/C mice were randomly assigned to 6 groups:phosphate buffer saline(PBS)group(PBS+PBS);blank group(PBS+empty microbubbles);lipopolysaccharide(LPS)group(LPS+PBS);ARDS group(LPS tempty microbubbles);control group(PBS+sFlt microbubbles);and treatment group(LPS+sFIt microbubbles).After administration of LPS or PBS in the corresponding groups,the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation.Then the lungs were irradiated with ultrasound,which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted.The lung injury score,lung wet/dry ratio(W/D),liver and kidney functions,and the mortality of the mice in all groups were investigated at the predetermined time point.The difference in mortality between groups was examined by Fisher test.Other data were analyzed by onc-way analysis of variance(ANOVA).A value of P<0.05 indicates that the difference was significant.The results showed that the PaO2 levels were normal in the PBS group,the blank group,and the control group.The LPS group and ARDS group showed significant hypoxia.PaO2 was improved significantly in the treatment group.The lung injury score and W/D were normal in the PBS group,the blank group,and the control group.The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group(P<0.05).The mortality rate of the ARDS model was 60%(95%confidence interval 47.5%-72.5%),and that with sFlt-targeted microbubbles was significantly lower at only 40%(95%confidence interval 27.5%-52.5%,P<0.05).It was concluded that anti-VEGF with sFIt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively.It might be a suitable therapeutic tool for the treatment of ARDS.

Enhanced thermal- and impact-initiated reactions of PTFE/Al energetic materials through ultrasonic-assisted core-shell construction

A facile and economical approach was developed for the large-scale production of powdered core-shell structured PTFE/Al (CS-PA) energetic materials through ultrasonic-assisted mixing. The low-cost micrometer-sized PTFE and Al particles were used as starting materials. Under high-power ultrasonic waves, the PTFE powder was dispersed into nano-to sub-micrometer-sized particles and then encapsulated the Al microparticles to form the core-shell structure. The heat of combustion, burning rate, and pressurization rate of the powdered CS-PA were measured. The thermal-initiated reaction behavior was further evaluated using thermogravimetry-differential scanning calorimetry. Subsequently, the bulk CS-PA with a uniform microstructure was obtained via cold isostatic pressing of the powdered CS-PA followed by vacuum sintering. For the bulk CS-PA, the quasi-static compression behavior was characterized, and the impact-initiated reaction processes were conducted using the Split Hopkinson Pressure Bar (SHPB) and evaluated by a high-speed camera. Compared to physically mixed PTFE/Al materials, the powdered and bulk CS-PA demonstrated enhanced thermal- and impact-initiated reaction characteristics respectively, proving the effectiveness of our approach for constructing core-shell structures.